Tau PET Longitudinal Substudy Associated With: A Double-Blind, Placebo-Controlled Parallel-Group Study in Preclinical PSEN1 E280A Mutation Carriers Randomized to Crenezumab or Placebo, and in Non-randomized, Placebo-treated Non-carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Crenezumab in the Treatment of Autosomal-Dominant Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Annualized Rate of Change in Tau Burden
研究概览
简要总结
This substudy will evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352). Participants will receive up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of [18^F]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrolled in main Study NCT01998841 (GN28352).
排除标准
- •Contraindication to PET scan procedures, possibly including, but not limited to current, past, or planned participation in studies involving radioactive agents, including the main Study NCT01998841 (GN28352) and this Tau PET substudy, such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.
研究组 & 干预措施
[^18F]GTP1 in Mutation Carriers: Crenezumab
Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
干预措施: Crenezumab (Drug)
[^18F]GTP1 in Mutation Carriers: Crenezumab
Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
干预措施: [^18F]GTP1 (Other)
[^18F]GTP1 in Mutation Carriers: Placebo
Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
干预措施: Placebo (Drug)
[^18F]GTP1 in Mutation Carriers: Placebo
Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
干预措施: [^18F]GTP1 (Other)
[^18F]GTP1 in Non-carriers of Mutation: Placebo
Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
干预措施: Placebo (Drug)
[^18F]GTP1 in Non-carriers of Mutation: Placebo
Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
干预措施: [^18F]GTP1 (Other)
结局指标
主要结局
Annualized Rate of Change in Tau Burden
时间窗: Baseline up to Week 149
Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using \[18F\]GTP1 Tau PET. The annualized rate of change in tau burden from the first \[18F\]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement.
次要结局
未报告次要终点